Differential block of pain sensibility, without impairment of motor function is often desired, either short-term or long-term. However, reliable differential peripheral nerve fiber conduction block is not presently available. The local anesthetics that have been applied for this purpose all act by inhibiting sodium conductance, an effect that shows no clear-cut predilection for slowly conducting axons such as those that transmit nociception from the periphery. At the compound action potential (CAP) level we have recently demonstrated resersible or irreversible differential interruption of conduction by five other types of agencies; glucose deficiency, oxygen deficiency, 'pump' inhibition, potassium channel block, hypoosmotic neural swelling, each with a different differential action on CAP components. However, uncertainties inherent in CAP must be resolved before an accurate appraisal of the clinical utilizability of these agencies, singly or in combination, can be performed. It is necessary to determine and compare at the unit level and in relation to conduction velocity of the concentration or intensities that block conduction in individual axons of all major size groups. This hitherto dauntingly laborious undertaking has become practical with the accession of a model in which the smallest fibers are as easy to test individually as the large ones. It consists of recording extracellularly from the individual cell bodies of afferent axons; the somata in the ganglion are of uniform size and much larger than even a large axon. One can thus apply a drug to the attached nerve and pick out the effect on the individual axon attached on the cell body, the size of the axon being characterized by the latency of a stimulated impulse. Executed on the nodose ganglion and vagus nerve of rabbit, this technique will be used to ascertain the critical concentrations of each of the above agencies required for reversible and irreversible block of individual axons in each of seven conduction velocity groups. Electrophysiological measurments and a novel pharmacokinetic computation will be used to determine the exact value for each axon. In conjunction with observations by electron microscopy this will lay the basis for future multifactorial quantitative approach to differential control of small and large fiber block of peripheral nerves, both for long-term relief of incurable pain and short-term management of acute pain, for example in childbirth.